These

such as leukemia, gout, and lithemia in its widest sense. granules are supposed to be significant of disintegration of the nuclei in the process of uric-acid formation. Their nature and significance, however, are unsettled. Occasionally vacuolization and fatty degeneration of leukocytes are observed, and sometimes, as in infectious fevers and in suppuration, glycogen may be found in abnormal quantities. In cover-glass preparations the leukocytes are sometimes found broken or fragmented, and this doubtless occurs to some extent in the circulating blood.

PATHOLOGIC CHANGES IN THE PLASMA. Various disorders of the plasma have been studied. These are mainly of a chemical sort, and consist of the presence of abnormal substances or of normal constituents in excessive quantity. Urea is present in large quantities in some cases of nephritis and uremia, and older authorities believed the symptoms of uremia due to the presence of this substance. This view is no longer held. Urie acid occurs in small quantities in health; but in large quantities in gout, leukemia, leukocytosis, and other disorders of the blood. The xanthin bases may be present in considerable quantities in the same cases. Glycogen or grape-sugar is found in excessive quantities in diabetes and, according to some observations, in cases of carcinoma. Levulose and other carbohydrates are rare constituents of the plasma. Fatty acids may be present in leukemia, diabetes, acute yellow atrophy of the liver, and some other diseases. The quantity of sodium in the plasma increases in anemic diseases.

Certain changes occur in the plasma or serum in anemic diseases, as a result of which the globulicidal character is increased. The nature of these changes is obscure. The presence of toxic substances the result of bacterial action is referred to in the discussion of bacteria.

Hypertonicity of the serum is a term indicating that the salinity of the plasma or serum is such that the blood may be somewhat diluted without destruction of the corpuscles. By graduated dilutions the degree of hypertonicity may be estimated, and is found less in certain diseases than in health (see Isotonicity of the Red Corpuscles).

Hyperinosis and hypinosis are terms designating increased and decreased capability for fibrin-formation. The former is met with at times in chlorosis, leukemia, or other anemic affections, and in certain infectious diseases. The latter is notably present in leukemia and some cases of hemolysis. There has been much theorizing in regard to these conditions, but very little knowledge of practical importance has been acquired.

PLETHORA.

Plethora is the name applied by the older writers to a condition in which the total quantity of blood was supposed to be excessive.

It is now recognized that plethora is much less frequent and permanent than was formerly believed. Several varieties were described.

Plethora vera was the name given to the condition in which the quantity of the blood was supposed to be increased without change in its quality. Persons supposed to have this condition are described as robust, with high color and vigorous circulation. They are generally individuals living in luxury. The term "fullblooded" is still applied, but it is recognized that the fulness of the superficial vessels is the result of peculiarities of the circulation rather than of increase in the quantity of blood.

Plethora apocoptica, is the term given to conditions in which there is local increase in the blood.

Plethora hydremica is a condition in which the total quantity of the blood is increased by dilution. This was regarded as frequent in cases of cachexia, after hemorrhages, etc.

Experimental evidence might be referred to to substantiate the view that plethora in the strict sense does not often occur as a lasting condition. Temporary plethora is produced by the drinking of large quantities of liquid, but the excretory organs soon dispose of this excess.

OLIGEMIA.

Oligemia is a term indicating reduction in the quantity of blood. This is met with temporarily after hemorrhage, but very soon serous liquid from the tissues enters the blood-vessels and restores the original quantity. At the time of the hemorrhage the quantity may be immediately reduced to a very great degree without causing death. Serious consequences are averted by the activity of the vasomotor system, the blood-vessels accommodating themselves by contraction to the reduced quantity of blood. Subsequently when liquid of the tissues is absorbed into the bloodvessels the latter dilate and their natural volume is soon restored. The blood, however, becomes hydremic, or watery. Oligemia or quantitative anemia may possibly occur in certain cachectic and anemic diseases, but this has not been proved, and the relative proportion between the mass of blood and the weight of the body is certainly not much disturbed in any case.

HYDREMIA AND ANHYDREMIA.

Hydremia, a diluted or watery condition of the blood, may occur from excessive consumption of water, but active excretion of liquid soon restores the blood to its previous condition. Hemorrhage leads to hydremia in the manner above described; and in the chronic anemias there is possibly some dilution of the serum. It has never been shown, however, in any of the many experiments made to determine this point, that the plasma in anemias is less rich in solid constituents than normal plasma. The reduction in

solid matter in the blood as a whole is due to the diminution in the number of red corpuscles and changes in their composition.

Anhydremia is a condition in which the plasma of the blood is thickened by the loss of watery elements. This may occur in consequence of excessive sweating or excessive discharge of water from the bowels, kidneys, etc. The number of red corpuscles in a given bulk of blood increases. The specific gravity and the solid residue of the plasma of the blood as a whole increase correspondingly.

LIPEMIA.

Lipemia is a pathologic condition in which fat occurs free in the blood-plasma. Fat is always present as a normal constituent of blood, and is in slight excess during the process of digestion. Lipemia occurs in cases of chronic nephritis, diabetes, pulmonary tuberculosis, alcoholism, and some other conditions, and may reach marked grades of severity. The blood may have a milky appear

FIG. 143.-Blood from a case of lipemia, stained with osmic acid: upper half of field cleared with oil of turpentine; lower half shows the fat-droplets and granules stained with osmic acid between the blood corpuscles; enlargement, 100 diameters (after Gumprecht: Deutsch med Woch., Sept. 27, 1894).

ance to the naked eye, and under the microscope highly refractive droplets or granules are observed. The latter stain black with osmic acid (Fig. 143).

MELANEMIA.

cases of malaria and certain other fevers. The pigment may be free in the plasma in the form of yellowish or blackish granules; or may be found as small particles in the leukocytes.

HEMOCYTOLYSIS-HEMOGLOBINEMIA.

Definition. Hemocytolysis is the term applied to the conditions in which the red blood-corpuscles are destroyed. The name hemolysis is generally employed in the same sense, though it refers to destruction of all of the elements of the blood. In this condition hemoglobin is liberated and is dissolved in the plasma. this the term hemoglobinemia is applicable, but the name methemoglobinemia is more appropriate, as the hemoglobin is usually present in the serum in this altered form.

То

Etiology.-Hemolysis constantly takes place in the liver, the coloring-matter of the blood being converted into bile-pigments. Pathologic hemolysis results from the action of various infectious and toxic agents. It occurs in the course of severe malaria, relapsing fever, pneumonia, and various hemorrhagic infections; and is occasioned by many poisons (see Blood-poisons). Excessive cold may be a contributing cause, as seems to be the case in some instances of paroxysmal hemoglobinuria (q. v.).

Pathologic Anatomy. The blood may present striking morphologic changes in the red corpuscles, such as microcytosis, megalocytosis, poikilocytosis, fragmentation, and vacuolation. Shadow-corpuscles may be abundant, and in the later stages of the process beginning regeneration of the blood causes the presence of nucleated red corpuscles. The blood as a whole is often quite dark in color.

Associated changes are frequently met with in the liver, kidneys, and skin. The hepatic cells are often swollen and more or less degenerated and bile-stained. Excessive production of bile (polycholia) may occur. This over-production, with the swelling of the hepatic cells and the consequent obstruction of the biliary channels, occasions reabsorption of bile and consequent jaundice (so-called hematogenous jaundice). The excess of hemoglobin, which cannot be disposed of by the liver, may be excreted in the urine (hemoglobinuria). Sometimes hemoglobin-infarcts are met with in the renal tubules ; and thrombosis of the renal or other bloodvessels is occasionally observed. Acute nephritis is a rare result.

Pathologic Physiology.-Hemocytolysis leads to more or less pronounced disturbance of the internal or tissue respiration, as the altered hemoglobin is incapable of carrying oxygen. Dyspnea and various nervous symptoms are the result. The liberation of cellular constituents (from destruction of the red and white. corpuscles) occasions increased coagulability of the blood and the formation of thrombi (ferment-intoxication). Fever and other general symptoms may be due to the same cause.

POLYCYTHEMIA.

Polycythemia, or erythrocytosis, the condition in which the number of red corpuscles in a given bulk of blood is increased, may be actual or relative. Actual polycythemia is that in which there is over-production of red corpuscles; this is probably rare. Relative polycythemia is due to decrease in the quantity of the plasma. It is met with in a variety of conditions, including certain cardiac diseases, with slow failure of compensation, and especially in congenital cyanosis; in residents of high altitudes; in the new-born; and in cases of cholera or other diseases in which liquid discharges cause inspissation of the blood. The explanation of the increased number of corpuscles in some of these conditions has occasioned considerable controversy. Some have held that the number of corpuscles (at high altitudes, for example) increases actually rather than relatively, for the purpose of furnishing a greater oxidizing surface, but this has not been proved. It is more likely that the increased number of corpuscles is caused by changes in their distribution in the circulation. In evidence of this it may be pointed out that the number of corpuscles in dependent parts, such as the foot, is greater than normal. In cardiac disease and in persons living at high altitudes it is not improbable that similar stagnation of the corpuscles in the peripheral tissues takes place.

LEUKOCYTOSIS.

The term leukocytosis is given to a more or less transient increase in the number of leukocytes, the polymorphonuclear forms being usually in excess. Sometimes leukocytosis is continuous or chronic, and sometimes the excessive number of leukocytes is due to increase in the mononuclear elements rather than the polymorphonuclear.

Etiology. The causes of leukocytosis are varied. It is generally observed as a normal condition in the new-born, the number of corpuscles remaining in slight excess during the first year of life. It also occurs in many cases of pregnancy; and is quite constant during the period of digestion in healthy persons, proteid food being more striking in the effect than a farinaceous or mixed diet. In some diseases of the stomach post-digestive leukocytosis seems not to occur.

Inflammatory and Infectious Leukocytosis.-Among the strictly pathologic forms of leukocytosis the most important are those due to inflammations and infections of various kinds. Croupous pneumonia occasions considerable increase of leukocytes in most cases, and this is continuous until the final decline of the fever. Suppurations of all kinds act in a similar manner. Inflammations of the scrous membranes-peritonitis, pleurisy, meningitis-may